RESUMEN
The abnormal increase of Oddi sphincter pressure and total bile duct pressure may play an important role in the formation of cholesterol stones, but the specific molecular mechanism is still unclear. This study aims to investigate it through in vitro and in vivo experiments. A mouse model of Oddi sphincter dysfunction was constructed by stone-inducing diet. We compared the two groups with PKC-α inhibitor GÖ6976 and PKC-α agonist thymeleatoxin. Oddi sphincter pressure and total bile duct pressure were measured. Biochemical analysis of total cholesterol, bile acid and bilirubin was then conducted. The histopathologic changes of bile duct were observed by HE staining and the ultrastructure of liver cells and surrounding tissues was observed by transmission electron microscopy. Through the above experiments, we found that the change of PKC-α expression may affect the formation process of gallstones. The relationship between PKC-α and ABCB11 was further verified by in vitro and in vivo experiments. Our results suggest that ABCB11 and PKC-α are co-expressed in the tubule membrane of hepatocytes and interact with each other in hepatocytes. The high cholesterol diet further enhances the activation of PKC-α and thus reduces the expression of ABCB11. The formation of cholesterol stones is associated with the down-regulation of ABCB11 expression in the tubule membrane of hepatocytes due to kinase signaling. This is the first study to demonstrate that sphincter of Oddi dysfunction induces gallstones through PKC-α inhibition of ABCB11 expression.
RESUMEN
Biliary Sphincter of Oddi dysfunction (SOD) is one of the main causes of post-cholecystectomy pain. In this review, we aimed to provide an update on the current knowledge on biliary SOD, with an emphasis on diagnostics and therapy. Overall, current but scarce data support biliary sphincterotomy for patients with type 1 and 2 SOD, but not for type 3. However, sphincterotomy is associated with post-treatment pancreatitis rates of from 10% to 15%, thus calling for improved diagnostics, patient selection and treatment modalities for SOD. The role of pharmacologic therapy for patients with SOD is poorly explored and only two randomized controlled trials are available. Currently, studies comparing treatment outcomes are few. There is an unmet need for randomized sham/placebo-controlled clinical trials related to both pharmacological and non-pharmacological treatments of SOD.
RESUMEN
Opium addiction is rampant in Western Rajasthan and probably has the highest number of opium addicts in the world. The study envisages upon the presentation, diagnosis and various postoperative complications in surgically ill opium addicts vis-à-vis non addicts. The study is purported to benefit clinicians dealing with opium addict patients. The prospective cohort study was conducted at Mahatma Gandhi Hospital, Jodhpur between December 2004 and February 2006 and included cohorts of 71 opium addict and 50 non-addict patients admitted in various surgical wards. The study focused on presentation and the post-surgical complications encountered in these patients vis-à-vis others. The results thus obtained were evaluated statistically (mean±SD, SEM, two tailed t test, chi-square test), p value of <0.05 was considered as significant. A thorough comparative analysis revealed that opium addict patients had a significantly higher incidence of postoperative respiratory, cardiovascular, systemic and local complications. The requirement of analgesics and duration of hospital stay were also significantly higher as compared to control group. The work concludes that opium addicts suffer a much higher degree of postoperative morbidity as compared to non-addicts.
